tbuckley/cabot-search huggingface dataset:
Abstract 14147: Septal Longitudinal Strain Predicts Long-Term Mortality in Patients With Acute Pulmonary Embolism
Authors: Caroline L Bjerregaard, Sif M Rasmussen, Ali Shabib, Niels Toender, Thomas Fritz-Hansen, Tor Biering-Sørensen, Flemming J Olsen
Journal: Circulation (2022)

Background Acute pulmonary embolism (PE) is associated with an increased risk of short- and long-term mortality. Since interventricular septal systolic function contributes to a third of right ventricular (RV) cardiac output, we sought to investigate the potential value of septal strain in PE. Methods This was a retrospective cohort study of patients admitted with acute pulmonary embolism. Patients underwent echocardiography during admission and included left ventricular (LV) speckle tracking, by which global longitudinal strain (GLS) and regional strain were acquired. Multivariable adjustments were made for age, sex, simplified PE index (sPESI), abnormal cardiac biomarkers (troponin or proBNP) and RV systolic function. The endpoint was all-cause death. Results The cohort consisted of 186 patients (mean age 68 years, 54% men), of whom 49 (26%) died during a median follow up of 3.5 years (IQR: 2.9-6.7 years). All LV systolic measures were univariable predictors of death (LVEF: HR: 1.04 (1.02-1.06), per 1% decrease; GLS: HR: 1.15 (1.07-1.22), per 1% absolute decrease; septal strain: HR: 1.15 (1.08-1.23), per 1% absolute decrease] (figure). RV systolic function was also associated with death [TAPSE: HR: 1.06 (1.01-1.12), per 1mm decrease). After multivariable adjustments, only septal strain remained significantly associated with outcome (HR: 1.09 (1.01-1.19), p=0.029, per 1% absolute decrease). Furthermore, septal strain significantly increased C-statistics when added to a base model of sPESI score, abnormal biomarkers and presence of hypotension (base model C-stat: 0.76; base model and septal strain C-stat: 0.83, p for increment = 0.006). Conclusion Septal strain is associated with death in acute PE and provides prognostic information beyond conventional risk assessment.
Abstract 13454: Utilization Rate and Outcome Trends for Watchman Procedure - Nationwide Analysis
Authors: Muhammad Qudrat Ullah, Muhammad Usman Almani, Muhammad Usman, Aviral Vij
Journal: Circulation (2022)

Introduction: Left atrial appendage closure is increasingly offered to patients with atrial fibrillation who are poor candidates for long-term anticoagulation. We set out to determine the utilization rates and adjusted outcome trends for the WATCHMAN procedure. Methods: Data were extracted from the National Inpatient Sample (NIS) 2015 through 2019 Database. The NIS was searched for atrial appendage closure in adult patients (age ≥ 18) using ICD 9 and 10 codes. Outcomes of interest were utilization rates of WATCHMAN procedure through time, trends of adjusted mean length of stay (LOS), and adjusted mean cost. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. STATA software was used for analysis. Results: There were 63,190 WATCHMAN procedures performed from 2015 through 2019. The mean patient age was 76 years, and 58% were males. The utilization rates of the WATCHMAN procedure steadily increased from 1800 in 2015 to 26,915 in 2019 (the rise was steeper for females than males and for Caucasians than African Americans). The adjusted mean LOS decreased from 3.4 days to 1.4 days, trend p&lt;0.001. No statistically significant linear trend was observed in terms of adjusted mean hospital cost (32784$ in 2014 vs. 27385$ in 2019, trend p=0.071). Conclusions: There has been a steady rise in the use of WATCHMAN procedure in the United States, more so in females than males and in Caucasians than African Americans. Over the years, there has been a decrease in LOS for WATCHMAN hospitalizations, however, the hospital cost remained unchanged.
Abstract 14011: Rare Variants in GUCY1A3 Gene Contribute to Hypertension via NO/cGMP Pathway
Authors: Chen Li, Jing Wang, Xing Chao, MInjie Lu, Yuming Zhu, Xueyi Wu, Yibing Shao, Yubao Zou, lei song, Jizheng Wang
Journal: Circulation (2022)

Hypertension is a leading risk factor for cardiovascular events and considered as a complex genetic disease. Previous studies have revealed many common variants relevant to hypertension. However, the contributions of rare variants and the underlying mechanisms are still poorly understood. Through a case-control study with whole-exome sequencing, we found that rare nonsynonymous variants in GUCY1A3 gene were enriched in the patients with early-onset hypertension. To assess the effects of rare variants of GUCY1A3 , a knock-in mouse model carrying a variant corresponding to Pro637His in human GUCY1A3 was generated, and the blood pressure (BP) was measured by telemetry.The baseline systolic BP of both homozygous (P637H +/+ ) and heterozygous (P637H + )mice were higher than their wide-type (WT) littermate controls. After administration of eNOS inhibitor, BP elevated in all genotypes, and the P637H +/+ and P637H + mice had profoundly higher BP than WT. The vascular dysfunction in mutated mice was determined as contraction curves of aorta ring elevated earlier and higher, and relaxation curves decreased later than WT rings. Furthermore, compared to WT mice, the protein levels of sGCα1 and sGC in both P637H +/+ and P637H + mice were decreased both at baseline and after NO inhibitor treatment, and the cGMP levels were also significantly decreased. Consistenly, the activity of cGMP-dependent protein kinase1 (cGK-1) was supressed and the phosphorylation of its downstream substrate, myosin light chain, was increased in knock-in mice. Finally, the inhibitory effect on sGC proteins expression and NO/cGMP pathway activity were also observed in vitro on other 5 rare nonsynonymous variants of GUCY1A3 . In conclusion, our results demonstrate that GUCY1A3 defects contribute to hypertension by reducing the activity of NO/cGMP pathway, and support that rare varaints are important components of the genetic architecture of hypertension.
Abstract 128: Yield Of Computed Tomography After Non-Traumatic Out-of-Hospital Cardiac Arrest
Authors: Jonathan Tam, Christopher Soufleris, Cecelia R Ratay, Adam N Frisch, Jonathan Elmer, Kate Flickinger, Clifton W Callaway, Patrick J Coppler
Journal: Circulation (2022)

Background Computed tomography (CT) can identify the etiology of cardiac arrest and injuries related cardiopulmonary resuscitation (CPR). Diagnostic yield of CT has only been characterized in a few small cohort studies with varied imaging practices. Purpose To determine diagnostic yield of CT imaging after out-of-hospital cardiac arrest (OHCA). Methods We included non-traumatic OHCA patients treated at a single center February 2019 to February 2021. Our practice during the study period was to obtain unenhanced head CT in all comatose patients and CT of the cervical spine, chest, abdomen, and pelvis in most cases. We abstracted patient age and sex, CPR duration, and initial neurological examination from our prospective registry. We reviewed clinical records and identified CT imaging obtained within 24 hours of arrival. We reviewed radiology reports, and summarized findings for each body region. Results We included 505 subjects. Mean age was 60 [SD 16] years and 144 (29%) had an initial shockable rhythm. Median CPR duration was 21 [IQR 12-35] minutes and 448 (89%) subjects were comatose on presentation. Almost all subjects had brain imaging (n=481, 95%), of which 33 (7% [95% CI 5-9%]) had intracranial hemorrhage and 157 (33% [95% CI 28-37%]) had cerebral edema. Fewer subjects had a cervical spine CT (n=202, 40%) though 4 (2% [95% CI 0-4%]) had vertebral fractures. Most subjects had a CT of the chest (n=396, 76%), and abdomen and pelvis (n= 347, 69%). Identified chest pathologies included rib or sternal fractures (222, 56% [95% CI 51-61%]), pneumothorax (27, 7% [95% CI 5-10%]), aspiration or pneumonia (300, 76% [95% CI 71-80%]), mediastinal hematoma (18, 5% [95% CI 3-7%]), and pulmonary embolism (13, 3% [95% CI 2-6%]). Significant abdomen and pelvis findings were bowel ischemia (23, 7% [95% CI 4-10%]), and splenic or liver laceration (7, 2% [95% CI 1-4%]). Conclusions Cross sectional imaging identifies clinically important pathology that informs early management.
Abstract 14086: Do Outcomes Differ Between STEMI and NSTEMI Cardiogenic Shock?
Authors: Mohit Pahuja, Shashank S Sinha, Rachna Kataria, Vanessa Blumer, Jaime Hernandez-Montfort, Manreet Kanwar, Arthur R Garan, Yijing Zhang, Neil Harwani, BORUI LI, Paulina Baca, Fatou Dieng, Jeffrey Marbach, Adnan Khalif, Saraschandra Vallabhajosyula, Sandeep Nathan, Daniel Burkhoff, Navin K Kapur
Journal: Circulation (2022)

Background: Acute myocardial infarction relatedcardiogenic shock (AMI-CS) is a multifactorial syndrome with high morbidity andmortality. Contemporary, real-world data comparing outcomes among patients withST-elevation myocardial infarction related CS (STEMI-CS) versus non-STEMI(NSTEMI-CS) is lacking. Methods: Using data from 17 sites from the CardiogenicShock Working Group (CSWG) registry, we compared the clinical characteristics,hemodynamic, and metabolic profiles between STEMI-CS and NSTEMI-CS patients. Between 2016 to 2020, data from 1110 adultpatient hospital admissions with the diagnosis of AMI-CS were collected. Patientswith available data within 24 hours of admission were stratified according to baselineand maximum SCAI Stage. We performed comparison between STEMI vs NSTEMI groupusing one-way Anova analysis. Results: Among 1,110 patients with AMI-CS, 731(65.8%) had STEMI-CS and 379 (34.2%) had NSTEMI-CS. Most patients were male andwhite. Compared with NSTEMI-CS patients, STEMI-CS patients were younger (63.8±12.3 vs 69.2 ± 12.3, p&lt;0.001). Overall unadjusted in-hospital mortality was41%. Mortality was similar among STEMI-CS and NSTEMI-CS patients (43% vs 39%,p=0.23). Patients with out-of-hospital (OHCA) or in-hospital cardiac arrest (IHCA)had higher in-hospital mortality (55% vs 39%, p =0.002; 62%% vs 33%, p&lt;0.001, respectively) (Fig 1A).Shock severity defined by SCAI Stage within 24 hours of admission (baseline)and throughout hospitalization (maximum) directly correlated with in-hospitalmortality in both STEMI- and NSTEMI-CS (Fig 1B). Conclusion: We report one of the largest contemporary analysesspecifically comparing outcomes with STEMI-CS and NSTEMI-CS. Cardiac arrest is an important determinant ofmortality and SCAI Stages are directly associated with poor outcomes in bothcohorts.
Abstract 14202: Prenatal Diagnosis Influences Birth Characteristics and Subsequent Postoperative Outcomes in Transposition of Great Arteries
Authors: Siva P Namachivayam, warwick w Butt, Christian P Brizard, Johnny Millar, Jenny Thompson, Sue P Walker, Michael Cheung
Journal: Circulation (2022)

Background: Prenatal diagnosis of transposition of great arteries (TGA) is expected to improve postoperative outcomes after neonatal arterial switch operation (ASO); however published reports give conflicting results. We aimed to determine the association between prenatal diagnosis and postoperative outcomes after neonatal ASO. Methods: Cohort study conducted among 243 newborns with TGA (70 % prenatally diagnosed) born mainly in 3 Australian states (Victoria, South Australia and Western Australia) between 2010 and 2019. Robust multivariable modelling was used to determine the influence of prenatal diagnosis on (a) birth characteristics and (b) post-operative outcomes. Mediation analysis estimated the extent to which prenatal diagnosis mediated its effects through gestational age. Results: Gestational age and birthweight centile were lower and small-for-gestational-age (birthweight &lt;10th centile) more common (11.8% vs 1.4%) in those diagnosed prenatally. Among births which followed labour induction or prelabour caesarean, prenatal diagnosis was associated with earlier gestational age at birth [mean (SD), 38.5(1.6) vs 39.2(1.4), P=0.01]. Among births which followed spontaneous onset of labour, prenatal diagnosis was associated with earlier gestational age at labour onset [38.2 (1.8) vs 39.2 (1.4), P = 0.01]. Prenatal diagnosis was associated with longer mechanical ventilation (incidence rate ratio: 1.74, 95% CI, 1.37 to 2.21), intensive care unit (1.70, 1.31 to 2.20) and hospital stay (1.37, 1.14 to 1.66) and also a greater need for postoperative extracorporeal membrane oxygenation. Gestational age at birth mediated up to 60% of the effect of prenatal diagnosis on postoperative outcomes. Conclusion: In this Australian study, prenatal diagnosis for TGA is associated with poorer postoperative performance after neonatal ASO and a large proportion of this effect is mediated by gestational age at birth. A higher proportion of newborns with a prenatal diagnosis were also small-for-their gestational age. Addressing factors associated with earlier gestational age at birth is likely to improve postoperative outcomes.
Abstract 12973: <i>Ulk1</i> Inhibition Ameliorates <i>Ttntv</i> Cardiomyopathy in Adult Zebrafish via Repairing Dysregulated Autophagy and Cellular Senescence
Authors: Ping Zhu, Jiarong Li, Yonghe Ding, Shahidul Islam, Xiaolei Xu
Journal: Circulation (2022)

Background: TITIN truncational variants (TTNtv) is the predominant genetic factor for dilated cardiomyopathy (DCM). Therapeutic development for TTNtv DCM has been confounded by allelic heterogeneity (AH), i.e. while truncations in the C-terminal A-domain (TTNtv-As) are pathogenic, truncations in the N-terminal Z-disc domain (TTNtv-Zs) are largely benign. Molecular mechanisms underlying AH remain elusive, partially because of the lack of an in vivo animal model. Objective: We enquire whether zebrafish is a faithful vertebrate model for deciphering AH in TTNtv DCM and for therapeutic development. Methods and Results: Through comparing phenotypes among a series of ttntv -As and ttntv -Zs in adult zebrafish, we detected DCM-like phenotypes only in ttntv -As but not ttntv -Zs. Similar to human TTNtv DCM and corresponding rodent models, zebrafish ttntv -As manifest decreased ejection fraction, enlarged heart size, myofibril dys-organization, compromised exercise capacity, and dysregulated autophagy. Moreover, we noted exaggerated cardiac senescence at the later stage of the pathogenesis of ttntv DCM. Because AH in autophagy dysregulation was also detected in homozygous ttntv-A zebrafish embryos, we screened autophagy genes and identified ulk1 inhibition that is able to repair the dysregulated autophagy. A similar repairing effect of ulk1 inhibition on dysregulated autophagy was noted in an adult heterozygous ttntv-A model, which is sufficient to attenuate the cardiac senescence and improve cardiac function. Conclusion: Our data suggested adult zebrafish as the first vertebrate model that is able to recapitulate AH in TTNtv DCM patients. Conserved phenotypes including autophagy dysregulation are recapitulated in this lower vertebrate model, while cardiac senescence has been suggested as a novel pathological event. Genetic studies in this animal strongly suggest that repairing autophagy dysregulation is a therapeutic avenue for TTNtv DCM, and identified ulk1 as a candidate therapeutic target gene.
Abstract 13730: Genotype-Phenotype Correlates in Recent-Onset Dilated Cardiomyopathy and Their Prognostic Implications
Authors: Milos Kubanek, Lenka Piherova, Alice Krebsova, Jana Binova, Martin Kotrc, Hana Hartmanova, Viktor Stranecky, Tomas Palecek, Anna Chaloupka, Ilga Grochova, Jan Krejci, Jana Petrkova, Vojtech Melenovsky, Stanislav Kmoch, Josef Kautzner
Journal: Circulation (2022)

Introduction: Recent-onset dilated cardiomyopathy (RODCM) is a disease of heterogeneous etiology and diverse clinical outcomes. Hypothesis: We hypothesized that the genotype of RODCM might correlate with left ventricular reverse remodeling (LVRR) and long-term clinical outcomes. Methods: A total of 386 RODCM patients (pts) [age 44±12 years, 277 males (72%), familial in 98 pts (25%)] with a history of symptoms less than six months underwent whole-exome sequencing (WES) where likely-pathogenic and pathogenic (class 4-5) disease-causing variants were identified. LVRR was defined as an improvement in left ventricular ejection fraction to &gt;50% or ≥10% absolute increase, with left ventricular end-diastolic diameter ≤33 mm/m2 or ≥10% relative decrease. In this prospective study, the primary outcome was the first event of all-cause death, heart transplantation or ventricular assist device. The secondary outcome included sudden cardiac death, resuscitated cardiac arrest or treated ventricular tachyarrhythmias. Results: WES detected class 4-5 titin truncated variants ( TTNtv ) in 69 pts (19%), class 4-5 non-titin variants (non- TTN ) (Figure) in 56 pts (14%), variants of unknown significance only in 103 pts (27%) and a negative result in 158 pts (40%). At 12 months, LVRR was assessed in 359 pts and was present in 171 pts (48%). Carriers of class 4-5 non- TTN variants developed LVRR less frequently than subjects with other genetic testing results (28% vs. 51%, p˂0.01). During a median follow-up of 55 months, the primary and secondary outcomes occurred in 79 pts (20%) and 50 pts (13%), respectively. Carriers of class 4-5 non- TTN variants had an increased risk of both primary [HR 2.36 (95% CI 1.32-4.20), p˂0.01] and secondary [HR 3.08 (95% CI 1.42-6.67), p˂0.01] outcomes as compared with genotype-negative pts. In multivariable models, genotype remained a strong predictor of both types of outcome. Conclusions: Among RODCM patients, carriers of class 4-5 non- TTN variants have an increased risk of death and progressive heart failure, and a higher long-term burden of life-threatening ventricular arrhythmias compared to genotype-negative subjects. Funding: Supported by the research grant of the Ministry of Health, Czech Republic: [NV19-08-00122] and IPO 00023001.
Abstract 13298: Racial and Ethnic Variation in ECMO Use, Failure to Rescue, &amp; Mortality in Pediatric Cardiac ICU Patients: A Multicenter Cohort Study From the Pediatric Cardiac Critical Care Consortium Registry
Authors: Marissa A Brunetti, Heather M Griffis, Michael L Obyrne, Andrew C Glatz, JING HUANG, Titus Chan, Kurt Schumacher, David Bailly, Yuliya Domnina, Javier J Lasa, Michael-Alice Moga, Hayden Zaccagni, Janet M Simsic, James W Gaynor
Journal: Circulation (2022)

Introduction: Previous studies have reported racial disparities in ECMO use. Using a clinical registry, we sought to determine if there was racial &amp; ethnic variation in ECMO use &amp;, if so, whether outcomes were mediated by differences in ECMO use. Methods: Multicenter, retrospective cohort study of the Pediatric Cardiac Critical Care Consortium (PC 4 ) clinical registry. Racial/ethnic categories included White, Black, Hispanic, Asian, &amp; other race (Native American, Pacific Islander, &amp; mixed race). Analyses were stratified by hospitalization type (medical vs. surgical). Multivariable logistic regression models adjusted for measurable confounders &amp; evaluated the association between race/ethnicity with ECMO use, failure to rescue (FTR), &amp; mortality. Analyses of outcomes were adjusted for ECMO use. Secondary analyses explored interactions between race/ethnicity, insurance, &amp; socioeconomic status with ECMO use &amp; outcomes. Results: From 8/1/14-1/31/19, 50,552 hospitalizations from 34 hospitals were studied. Across all hospitalizations, 2.9% (n=1467) included ECMO. In both surgical &amp; medical hospitalizations, Black race &amp; Hispanic ethnicity were associated with severity of illness proxies. In medical hospitalizations, race &amp; ethnicity were not associated with the likelihood of ECMO use. In medical hospitalizations, other race had higher adjusted odds of FTR (aOR 1.69 95% CI 1.06-2.70 p=0.03) &amp; higher adjusted odds of mortality (aOR 1.61 95% CI 1.22-2.12 p=0.001). For surgical hospitalizations, Black (aOR 1.24 95% CI 1.02-1.50 p=0.03) &amp; other race (aOR 1.50 95% CI 1.17-1.93 p=0.001) were associated with higher adjusted odds of ECMO use compared to Whites. No significant differences were found in FTR for surgical hospitalizations but hospitalizations of Hispanics had higher adjusted odds of mortality (aOR 1.31 95% CI 1.03-1.68 p=0.03). No significant interactions were demonstrated between race/ethnicity &amp; indicators of SES with ECMO use or outcomes. Conclusions: Black &amp; other race were associated with increased likelihood of ECMO during surgical hospitalizations. There were racial/ethnic disparities in outcomes not explained by differences in ECMO use. Efforts to mitigate these important disparities should include other aspects of care.
Abstract 14080: LINC02397 in Skeletal Muscle: A Marker of, and Therapeutic Target for, Chronic Limb Threatening Ischemia
Authors: Shohei YOSHIDA, Joseph McClung, Mehmet Koseoglu, Lauren Brewer, Joshua Heuslein, Brian H Annex
Journal: Circulation (2022)

Background: Chronic limb threatening ischemia (CLTI) is the most severe complication of peripheral arterial disease (PAD) and the leading cause of amputations for US adults. The response to reduced blood flow within ischemic muscle plays a role in determining disease outcome in PAD, but the response mechanisms have not been fully elucidated. Recently, long non-coding RNAs (lncRNAs) have been shown to regulate gene expression and modify disease. The objective of this study is to identify and characterize lncRNA that is differentially expressed in ischemic muscle in CLTI to serve as a therapeutic target in PAD. Methods: RNA sequencing (n=6/group) and whole transcriptome shotgun sequencing (WTSS n=15/group) from human muscle tissue in CLTI and healthy adults (HA) were performed to identify differentially expressed lncRNA candidates. qPCR (n=10/group) was performed on separate muscle samples to validate the findings. In-vitro experiments were conducted to examine which major cell type in muscle tissue likely expressed the candidate lncRNAs which were subsequently knocked down in cell types with the highest expression to determine function by qPCR, metabolic assay, and flow cytometry. Results: RNA-seq and WTSS analysis identified LINC02397, and qPCR confirmed LINC02397 was expressed significantly higher in CLTI patients (cT count 27.3±1.7 vs 34.1±1.4 in HA, p &lt;0.0001). Differentiation of monocytes isolated from human PBMCs to macrophages (a process triggered by inflammatory stimuli) increased expression of LINC02397 by 2 4 , the highest expression level among major cell types in muscle. In monocytes (THP-1 cells), PMA treatment induced a macrophage-like phenotype, and LINC02397 expression increased in conditions that trigger inflammatory activation: PMA, LPS, and hypoxia serum starvation. LINC02397 knockdown significantly downregulated inflammatory cytokines IL-1β and IL-6, CD86+ cells, and glycolysis. LPS-activated monocyte media increased the proliferative capacity of endothelial cells after knockdown, suggesting potential promotion of angiogenesis. Conclusions: LINC02397 is uniquely expressed in skeletal muscle of CLTI patients and may serve as a promising therapeutic via its ability to limit inflammation and promote angiogenesis.